Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.      

Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

Estimating the cost of expanding an apheresis program

To determine the cost of expanding blood product operations, the concept of marginal cost must be used. This article reports the development and implementation of a method of costing increases in collecting plasma using apheresis operations. The model takes into account the fact that certain resource inputs--notably, direct labor and machines--increase in discrete steps rather than in a continuous manner. To address this fact, a stepwise cost analysis function was developed, which related operating costs to the volume of apheresis collections. This function was used to predict the marginal costs of potential increases in the supply of plasma at a blood center in Canada. Differences were noted in the cost of plasma in Canada and the United States, much of which could be attributed to different standards regarding the volume of plasma per collection and to differences in pricing materials.     

Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion- associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one- way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA- GVHD.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Cytopathological and chemico‐physical analyses of smears of mucosa surrounding oral piercing

Oral Diseases (2010) 16 , 160–166 Objective: The aim of this comparative study was to analyze cytopathologically and chemico‐physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back‐scattered) scanning electron microscope (SEM) and X‐ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X‐ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.     

Impact of body mass index and tobacco smoking on outcome after open appendicectomy

Background:

The effect of body mass index (BMI) and smoking on the risk of perforated appendix and postoperative complications in patients undergoing open appendicectomy for acute appendicitis was studied.

Methods:

Record linkage was used to identify 6676 male construction workers who underwent open appendicectomy for acute appendicitis between 1971 and 2004. Multivariable binomial logistic regression analyses were performed.

Results:

After adjustment for age, calendar period and BMI, smoking was significantly associated with an increased risk of perforated appendicitis (PA) (P = 0·004). The relative risk was 1·29 (95 per cent confidence interval 1·11 to 1·50) among current smokers with more than 10 pack‐years of tobacco use. In patients with non‐perforated appendicitis (NPA), the relative risk of overall postoperative complications was significantly associated with BMI (P < 0·001), and was 2·60 (1·71 to 3·95) in obese patients and 1·51 (1·03 to 2·22) in current smokers with more than 10 pack‐years of tobacco use. In patients with PA, overweight, obesity and smoking status were not associated with an increased risk of overall postoperative complications.

Conclusion:

Perforation due to acute appendicitis was associated with current tobacco smoking. A BMI of 27·5 kg/m² or more and current smoking were associated with overall postoperative complications in patients with NPA. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.